5dvx: Difference between revisions
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==Crystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolution== | |||
<StructureSection load='5dvx' size='340' side='right'caption='[[5dvx]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DVX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.598Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvx OCA], [https://pdbe.org/5dvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dvx RCSB], [https://www.ebi.ac.uk/pdbsum/5dvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anti-cancer agents with some entering Phase I clinical trials. hCA IX is a transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical/biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible and its catalytic efficiency is suggested to be correlated directly with its stability between 3.0<pH<8.0 but not at pH>8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 A resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low pH tumor microenvironments, and may be applicable to determining pH-related effects on other enzymes. | |||
Structure of carbonic anhydrase IX is adapted for low pH catalysis.,Mahon BP, Bhatt A, Socorro L, Driscoll JM, Okoh C, Lomelino CL, Mboge MY, Kurian JJ, Tu C, Agbandje-McKenna M, Frost SC, McKenna R Biochemistry. 2016 Jul 20. PMID:27439028<ref>PMID:27439028</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5dvx" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Driscoll JM]] | |||
[[Category: Mahon BP]] | |||
[[Category: McKenna R]] | |||
[[Category: Socorro L]] | |||
Latest revision as of 01:02, 29 June 2023
Crystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolutionCrystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolution
Structural highlights
FunctionCAH9_HUMAN Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.[1] Publication Abstract from PubMedHuman carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anti-cancer agents with some entering Phase I clinical trials. hCA IX is a transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical/biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible and its catalytic efficiency is suggested to be correlated directly with its stability between 3.0<pH<8.0 but not at pH>8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 A resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low pH tumor microenvironments, and may be applicable to determining pH-related effects on other enzymes. Structure of carbonic anhydrase IX is adapted for low pH catalysis.,Mahon BP, Bhatt A, Socorro L, Driscoll JM, Okoh C, Lomelino CL, Mboge MY, Kurian JJ, Tu C, Agbandje-McKenna M, Frost SC, McKenna R Biochemistry. 2016 Jul 20. PMID:27439028[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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